Detecting selection in immunoglobulin sequences
Detecting selection in immunoglobulin sequences
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DOI：
10.1093/nar/gkr413
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发表时间：
2011-07-01
影响因子：
14.9
通讯作者：
Kleinstein, Steven H.
中科院分区：
文献类型：
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作者：
Uduman, Mohamed;Yaari, Gur;Kleinstein, Steven H.
通过分析实验衍生的免疫球蛋白（Ig）序列的突变模式来检测选择的能力是许多研究的关键部分。这些技术不仅有助于了解对病原体的反应，而且还有助于确定抗原驱动选择在自身免疫、B细胞癌和某些物种免疫前反应多样化中的作用。尽管它的重要性，定量选择在实验衍生序列充满了困难。统计测试的必要参数（例如在没有选择的情况下替换突变的预期频率）的计算是非常重要的，并且在分析多个序列时，结果不容易解释。我们已经开发了一个web服务器，它实现了我们之前提出的用于检测选择的聚焦二项检验。为了便于分析，网站整合了几个功能，包括使用IMGT比对进行V(D)J种系片段鉴定、批量提交序列和整合其他小组提出的额外测试统计。我们还实现了基于z分数的统计，在保持特异性的同时增加了检测选择的能力，并进一步允许对来自不同种系的序列进行组合分析。该工具可在http://clip.med.yale.edu/selection免费获得。
The ability to detect selection by analyzing mutation patterns in experimentally derived immunoglobulin (Ig) sequences is a critical part of many studies. Such techniques are useful not only for understanding the response to pathogens, but also to determine the role of antigen-driven selection in autoimmunity, B cell cancers and the diversification of pre-immune repertoires in certain species. Despite its importance, quantifying selection in experimentally derived sequences is fraught with difficulties. The necessary parameters for statistical tests (such as the expected frequency of replacement mutations in the absence of selection) are non-trivial to calculate, and results are not easily interpretable when analyzing more than a handful of sequences. We have developed a web server that implements our previously proposed Focused binomial test for detecting selection. Several features are integrated into the web site in order to facilitate analysis, including V(D)J germline segment identification with IMGT alignment, batch submission of sequences and integration of additional test statistics proposed by other groups. We also implement a Z-score-based statistic that increases the power of detecting selection while maintaining specificity, and further allows for the combined analysis of sequences from different germlines. The tool is freely available at http://clip.med.yale.edu/selection.